DESCRIPTION, OVERALL (provided by applicant): The University of Pennsylvania's Digestive Diseases Research Core Center (DDRCC), entitled Center for Molecular Studies in Digestive and Liver Diseases, has been funded since 1997. This competing grant proposal continues to unite investigators from multiple disciplines for integrated digestive and liver based research. The research base includes investigators organized in the following 3 interrelated scientific focus or affinity groups: (1) Development biology and genetics, (2) Immunobiology and host responses, and (3) Cell growth and differentiation. The research base consists of 55 members, with interrelated scientific programs, and represents a spectrum of departments, Centers, Institutes and Schools at the University of Pennsylvania. In addition, there is a young investigator base of 14 associate members, whose own individual programs and career development are nurtured by the Center. Center members are supported by $30,650,813 in digestive-diseases related NIH research funding, of which 42.12% is through NIDDK. A fundamental goal of our Center is to foster interdisciplinary research that leads to a cooperative understanding of the molecular and biochemical processes that form, regulate, and operate digestive tract, pancreatic and liver organs and their organizing tissues in health and disease. In this context, our intent is to utilize the Center as a means to develop innovative ideas by attracting and engaging established investigators into digestive and liver research. An equally important goal of the Center is to develop young investigators in this research. Four highly successful Scientific Core facilities are designed to provide digestive-specific services for the stimulation of collaborative research: Morphology, Molecular Biology/Gene Expression, Transgenic and Chimeric Mouse, and Cell Culture. An Administrative Core directs the fiscal and organizational aspects of the Center, including the coordination and publicity of the Scientific Cores, Pilot and Feasibility Grant Program, Academic Enrichment Program and Internal/External Advisory Committees. The Pilot and Feasibility Grant Program has been extremely successful for the promotion of new investigators in digestive research. Four proposals were selected based on their relevance to the Center's scientific focus and the priority of promoting digestive research among young investigators: (1) Role of protein-tyrosine phosphatase 1B (PTP1B) in obesity-related insulin resistance and non-alcoholic fatty liver disease (NAFLD);(2) An organotypic culture model of Barrett's esophagus;(3) Hematopoietic contribution to the gut vasculature;and (4) A p53/IGFBP1 regulatory circuit and liver cancer. Our DDRCC's aggregate functions maintain the digestive and liver research programs at the forefront of biomedical science.